Sickle Cell Disease
Conditions
Keywords
Pain, Biomarkers, 6 minute walk test, 5-HMF, Pharmacokinetics, Analgesic use, Sickle cell disease, Aes-103, SpO2, Anemia, Hemoglobin
Brief summary
Sickle cell disease (SCD) is a genetic blood disorder characterized by the presence of sickle-shaped red blood cells. In the U.S. and the U.K. this occurs primarily in persons of African origin. There is only one drug (hydroxyurea) approved to manage SCD, but it is not fully efficacious and can produce medically significant side effects. Aes-103 is being evaluated as a novel agent for the long term management of SCD. By directly reducing the sickling process, Aes-103 has a different mechanism of action than hydoxyurea. The active ingredient in Aes-103 is 5-hydroxymethyl furfural, a naturally occurring small molecule that is chemically related to glucose. This study will evaluate the safety and pharmacokinetic profile of two dosing regimens of Aes-103 for up to 28 days in up to 50 adult subjects with stable SCD compared with subjects receiving placebo.
Detailed description
This study will evaluate evaluate in subjects with stable SCD the safety, pharmacokinetic profile, clinical pharmacology actions and clinical activities of two dosing regimens of Aes-103 (1000 mg four times daily in Cohort A and a higher or lower dose given once daily or up to four times daily in Cohort B) given for up to 28 days in adult subjects with stable SCD compared with subjects receiving placebo.
Interventions
DRUGAes-103
The active ingredient in Aes-103 is 5-hydroxymethyl furfural (5-HMF). Aes-103 and matching placebo are administered in a liquid oral formulation.
OTHERPlacebo
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, aged 18-60 years old, inclusive * Diagnosis of SCD (hemoglobin SS) without hospitalization for pain crises or any other reason in the 14 days before enrollment * Have normal organ function as defined by direct bilirubin \<1.1 mg/dL (19 μmol/L), alanine transaminase (serum glutamic pyruvic transaminase) ≤120 IU/L, and Creatinine ≤1.3 mg/dL (115 μmol/L) * Have at least one of the following baseline values: hemoglobin level of \<10 g/dL, numerical pain rating scale (NPRS) score of ≥ 4, or 6-minute walk distance (6MWD) of \<500 m * If female, be nonpregnant and nonbreastfeeding and be surgically sterile or using an acceptable method of contraception throughout the study and for 3 months after the last dose of study medication * Have completed an outpatient screening visit consisting of medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs, hematology and chemistry tests, urinalysis, urine drug screen, urine or serum pregnancy test (females), hemoglobin electrophoresis, hepatitis B and C screening, and HIV serology * Be able to understand and have provided written informed consent including signature on an informed consent form approved by an institutional review board or independent ethics committee * Have provided written authorization for use and disclosure of protected health information * Agree to abide by the study schedule and to return for the required assessments
Exclusion criteria
* Have been hospitalized in the 14 days before enrollment, for any reason * Have evidence of clinically significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other disease that may interfere with the objectives of the study or the safety of the subject, or have been hospitalized in the past 6 months as a result of these conditions (for SCD-related morbidity, a minimum of 14 days from the last hospitalization is required)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Double-blind treatment period of 28 days (Day 1 to Day 28) | Number of participants with adverse events (AEs) reported during the double-blind treatment period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke. |
| Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | Placebo lead-in period of 14 days (Day -14 to Day -1) | Number of participants with adverse events (AEs) reported during the placebo lead-in period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke. |
| Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Post-treatment observation period of 21 days (Day 29 to Day 49) | Number of participants with adverse events (AEs) reported during the post-treatment observation period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke. |
| Number of Participants With Sickle-Cell Disease-related Symptoms | Placebo lead-in period of 14 days (Day -14 to Day -1), double-blind treatment period of 28 days (Day 1 to Day 28) and post-treatment observation period of 21 days (Day 29 to Day 49) | — |
| Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Throughout the study period (approximately 9 weeks) | Vital signs, 12-lead ECGs, clinical laboratory assessments, and physical and neurological examinations that were deemed clinically significant by the investigator in agreement with the sponsor study director. |
| PK: - Plasma AUC, Cmax, Tmax, and T1/2 of Aes-103 and Its Metabolite, HMFA - RBC Hemolysate AUC (0-8h), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of Hemoglobin Bound to Aes-103 | PK blood samples were to be taken within 10 minutes before dosing and 0.5, 1, 2, 4, and 6 hours after the first dose of study product on Days 1 and 7 and at the same time points on Day 28 (or early termination) | Pharmacokinetic endpoints in the study protocol were as follows:- - Plasma Area under curve (AUC), Maximum plasma concentration (Cmax), time at which Cmax observed (Tmax), and terminal half-life (T1/2) of Aes-103 and its metabolite, 5-hydroxymethyl-2-furoic acid (HMFA) - red blood cell (RBC) hemolysate Area under curve between 0 and 8 hours (AUC \[0-8h\]), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of hemoglobin bound to Aes-103 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28 | LDH levels were measured as a biomarker for intravascular hemolysis. The results are based on the LDH Total measurement. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Hemoglobin Levels - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28 | A clinical laboratory endpoint that reflects the amount of red blood cells present in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Reticulocyte Percent- Change From Baseline | At baseline, Day 1 and Day 7 during the double-blind treatment period | Category title includes number of participants with available data (n) for participants treated with study product. |
| Direct Bilirubin - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14, Day 21 and Day 28 | Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| LDH Isoform - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28 | — |
| C Reactive Protein Levels - Change From Baseline | At baseline, Day 1 and Day 7 during the double-blind treatment period | Category title includes number of participants with available data (n) for participants treated with study product. |
| Serum Ferritin Levels - Change From Baseline | At baseline, Day 1 and Day 7 during the double-blind treatment period | — |
| N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline | At baseline, Day 1, Day 7, Day 14 and Day 28 during the double-blind treatment period | Category title includes number of participants with available data (n) for participants treated with study product. |
| Body Weight - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28 | A negative change in body weight denotes a weight decrease, a positive change in body weight denotes a weight increase. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28 | Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline | Prior to dosing at baseline and on Day 49 of the post-treatment observation period | Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1. |
| Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | On last day of double-blind treatment period (Day 28) and on Day 49 of the post-treatment observation period | Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. |
| Exercise Tolerance: Cardiopulmonary Exercise Test [CPET] | On last day of double-blind treatment period (Day 28) | CPET was optional, based on capacity of participant to complete the test. |
| Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28 | A measure of the amount of oxygen in the blood. Oxygen saturation was determined by pulse oximetry. A pulse oximeter was placed over a nail polish-free finger nail to determine peripheral oxygen saturation (SpO2). Baseline was defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. A mean change from baseline \>0 indicates an increase in oxygen saturation, a mean change \<0 indicates a decrease in oxygen saturation. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period | Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period | Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline was defined as the most recent value obtained on the last day of the double-blind treatment period. Categories contain Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments | Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC | Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments | Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21. and Day 28. |
| Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments | Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC | Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments | Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 and Day 49. |
| Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments | Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC | Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments | Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Area under the curve (AUC) was computed using change from baseline (Day 28) in weekly average values at Day 35, Day 42 and Day 49. |
| Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | At baseline, Day 7 and Day 28 during the double-blind treatment period | Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | At baseline, Day 7 and Day 28 during the double-blind treatment period | Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline | At baseline and Day 49 during the post-treatment observation period | Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. |
| Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline | At baseline, Day 7 and Day 28 during the double-blind treatment period | Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline | At baseline and Day 49 during the post-treatment observation period | Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. |
| Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | At baseline and once weekly on Days 7, 14, 21, and 28 during the double-blind treatment period | Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. No values available for placebo group for Day 28. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Oxygen Binding p50/p20 Value - Change From Baseline | During the double-blind treatment period at baseline, Day 1, Day 4 and Day 7 | A measure of the ability of hemoglobin to bind oxygen. The p50 is the oxygen level at which 50% of the hemoglobin contains oxygen. The p20 is the oxygen level at which 20% of the hemoglobin contains oxygen. Baseline is defined as the most recent value obtained prior to start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Plasma Erythropoietin (EPO) Levels - Change From Baseline | At baseline and Day 28 during the double-blind treatment period | Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. EPO can be detected and measured in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Hematocrit Levels - Change From Baseline | Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28 | Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo. |
| Analgesic Use | Throughout the study period (approximately 9 weeks) | Analgesic use assessed with pain levels by numerical pain rating scale (NPRS) and brief pain inventory (BPI). |
| Reduction in Sickle Cell-specific Complications | Throughout the study period (approximately 9 weeks) | — |
Countries
United Kingdom
Participant flow
Recruitment details
Enrollment was conducted at one clinical site in the United Kingdom with referrals and/or patient identification from five other clinical sites in the United Kingdom.
Pre-assignment details
35 participants were enrolled. 10 failed screen and 2 were randomization failures. 23 started the 2-week, single-blind, placebo lead-in period (to obtain stable baseline values and to screen out participants who did not tolerate placebo or were not compliant with study procedures).
Participants by arm
| Arm | Count |
|---|---|
| Placebo lead-in Period Participants enrolled in a 14 day single-blind placebo lead-in received 4 times daily dosing of placebo | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Placebo Lead-in Period | Adverse Event | 2 | 0 | 0 |
| Placebo Lead-in Period | Other: Study Termination by Sponsor | 4 | 0 | 0 |
| Placebo Lead-in Period | Physician Decision | 2 | 0 | 0 |
| Placebo Lead-in Period | Withdrawal by Subject | 1 | 0 | 0 |
| Post-Treatment Observation Period | Other: Bad Veins | 0 | 1 | 0 |
| Post-Treatment Observation Period | Other: Study Termination by Sponsor | 0 | 2 | 0 |
| Treatment Period | Adverse Event | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo lead-in Period |
|---|---|
| Age, Continuous | 28 Years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 23 | 12 / 14 | 4 / 12 |
| serious Total, serious adverse events | 2 / 23 | 0 / 14 | 1 / 12 |
Outcome results
Primary
Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations
Vital signs, 12-lead ECGs, clinical laboratory assessments, and physical and neurological examinations that were deemed clinically significant by the investigator in agreement with the sponsor study director.
Time frame: Throughout the study period (approximately 9 weeks)
Population: safety analysis dataset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With Study Product | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Electrocardiogram T Wave Inversion | 0 clinically significant observations |
| Treatment With Study Product | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Transaminases Increased | 0 clinically significant observations |
| Treatment With Placebo | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Transaminases Increased | 0 clinically significant observations |
| Treatment With Placebo | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Electrocardiogram T Wave Inversion | 1 clinically significant observations |
| All Treated Participants | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Electrocardiogram T Wave Inversion | 0 clinically significant observations |
| All Treated Participants | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Transaminases Increased | 1 clinically significant observations |
| Post-treatment With Study Product Observation Period | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Electrocardiogram T Wave Inversion | 0 clinically significant observations |
| Post-treatment With Study Product Observation Period | Number of Clinically Significant Observations of Vital Signs, 12-lead ECGs, Clinical Laboratory Assessments, and Physical and Neurological Examinations | Transaminases Increased | 0 clinically significant observations |
Primary
Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period
Number of participants with adverse events (AEs) reported during the double-blind treatment period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Time frame: Double-blind treatment period of 28 days (Day 1 to Day 28)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | AEs leading to discontinuation | 1 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Serious AEs | 0 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Sickle-cell specific complications | 4 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Severe AEs | 0 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | AEs leading to death | 0 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Related AEs | 8 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Treatment-emergent AEs | 9 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Sickle-cell specific complications | 1 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Treatment-emergent AEs | 3 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Related AEs | 2 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Serious AEs | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Severe AEs | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | AEs leading to discontinuation | 1 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | AEs leading to death | 0 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Related AEs | 10 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | AEs leading to death | 0 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | AEs leading to discontinuation | 2 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Treatment-emergent AEs | 12 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Serious AEs | 0 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Sickle-cell specific complications | 5 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle Cell-specific Symptoms, During the Double-blind Treatment Period | Severe AEs | 0 participants |
Primary
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period
Number of participants with adverse events (AEs) reported during the placebo lead-in period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Time frame: Placebo lead-in period of 14 days (Day -14 to Day -1)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | Treatment-emergent AEs | 21 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | Related AEs | 12 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | Serious AEs | 2 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | Severe AEs | 2 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | AEs leading to discontinuation | 2 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | AEs leading to death | 0 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Placebo lead-in Period | Sickle cell-specific complications | 2 participants |
Primary
Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period
Number of participants with adverse events (AEs) reported during the post-treatment observation period. AEs included clinically-significant changes in vital signs, ECG, clinical laboratory assessments, physical and neurological examinations. Sickle cell-specific symptoms included the development of new skin ulcers, hospitalization or ambulatory acute care, intravenous analgesics visit for pain episodes (i.e., sickle-cell disease related pain), acute chest syndrome, priapism, and stroke.
Time frame: Post-treatment observation period of 21 days (Day 29 to Day 49)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Related AEs | 2 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | AEs leading to discontinuation | 0 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Severe AEs | 1 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Treatment-emergent AEs | 4 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Sickle cell-specific complications | 2 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | AEs leading to death | 0 participants |
| Treatment With Study Product | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Serious AEs | 1 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Severe AEs | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Treatment-emergent AEs | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Related AEs | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Serious AEs | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | AEs leading to discontinuation | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | AEs leading to death | 0 participants |
| Treatment With Placebo | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Sickle cell-specific complications | 0 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | AEs leading to discontinuation | 0 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Related AEs | 2 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Sickle cell-specific complications | 2 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | AEs leading to death | 0 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Severe AEs | 1 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Serious AEs | 1 participants |
| All Treated Participants | Number of Participants With Adverse Events, Including Sickle-cell Specific Symptoms, During the Post-treatment Observation Period | Treatment-emergent AEs | 4 participants |
Primary
Number of Participants With Sickle-Cell Disease-related Symptoms
Time frame: Placebo lead-in period of 14 days (Day -14 to Day -1), double-blind treatment period of 28 days (Day 1 to Day 28) and post-treatment observation period of 21 days (Day 29 to Day 49)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | Abdominal Pain - Sickle Pain | 0 participants |
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Pain | 3 participants |
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Disease Related Pain | 0 participants |
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | Vaso-Occlusive Crisis caused by Chest Infection | 1 participants |
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Crisis | 1 participants |
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | Intermittent SC Pain | 1 participants |
| Treatment With Study Product | Number of Participants With Sickle-Cell Disease-related Symptoms | Exacerbation of Sickle Cell (SC) Disease Pain | 1 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | Intermittent SC Pain | 0 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | Abdominal Pain - Sickle Pain | 1 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | Exacerbation of Sickle Cell (SC) Disease Pain | 1 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Disease Related Pain | 3 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Pain | 3 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Crisis | 0 participants |
| Treatment With Placebo | Number of Participants With Sickle-Cell Disease-related Symptoms | Vaso-Occlusive Crisis caused by Chest Infection | 0 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Crisis | 0 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | Intermittent SC Pain | 0 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | Exacerbation of Sickle Cell (SC) Disease Pain | 0 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | Vaso-Occlusive Crisis caused by Chest Infection | 0 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Pain | 1 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Disease Related Pain | 0 participants |
| All Treated Participants | Number of Participants With Sickle-Cell Disease-related Symptoms | Abdominal Pain - Sickle Pain | 0 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Disease Related Pain | 1 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Pain | 1 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Intermittent SC Pain | 0 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Abdominal Pain - Sickle Pain | 0 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Vaso-Occlusive Crisis caused by Chest Infection | 0 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Crisis | 0 participants |
| Post-treatment With Study Product Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Exacerbation of Sickle Cell (SC) Disease Pain | 1 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Vaso-Occlusive Crisis caused by Chest Infection | 0 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Crisis | 0 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Pain | 0 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Intermittent SC Pain | 0 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Exacerbation of Sickle Cell (SC) Disease Pain | 0 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | SC Disease Related Pain | 0 participants |
| Post-treatment With Placebo Observation Period | Number of Participants With Sickle-Cell Disease-related Symptoms | Abdominal Pain - Sickle Pain | 0 participants |
Primary
PK: - Plasma AUC, Cmax, Tmax, and T1/2 of Aes-103 and Its Metabolite, HMFA - RBC Hemolysate AUC (0-8h), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of Hemoglobin Bound to Aes-103
Pharmacokinetic endpoints in the study protocol were as follows:- - Plasma Area under curve (AUC), Maximum plasma concentration (Cmax), time at which Cmax observed (Tmax), and terminal half-life (T1/2) of Aes-103 and its metabolite, 5-hydroxymethyl-2-furoic acid (HMFA) - red blood cell (RBC) hemolysate Area under curve between 0 and 8 hours (AUC \[0-8h\]), Cmax, Tmax, and T1/2 of Aes-103 - Percentage of hemoglobin bound to Aes-103
Time frame: PK blood samples were to be taken within 10 minutes before dosing and 0.5, 1, 2, 4, and 6 hours after the first dose of study product on Days 1 and 7 and at the same time points on Day 28 (or early termination)
Population: PK data were not determined as the assay collection method was found to be faulty rendering all samples unevaluable.
Secondary
Analgesic Use
Analgesic use assessed with pain levels by numerical pain rating scale (NPRS) and brief pain inventory (BPI).
Time frame: Throughout the study period (approximately 9 weeks)
Population: Data not collected for this outcome measure. Study terminated early.
Secondary
Body Weight - Change From Baseline
A negative change in body weight denotes a weight decrease, a positive change in body weight denotes a weight increase. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Body Weight - Change From Baseline | Day 14 (n=8, 2) | 1.1 kg | Standard Deviation 0.8 |
| Treatment With Study Product | Body Weight - Change From Baseline | Day 4 (n=10, 3) | -0.3 kg | Standard Deviation 1.6 |
| Treatment With Study Product | Body Weight - Change From Baseline | Day 21 (n=6, 2) | 0.1 kg | Standard Deviation 1.4 |
| Treatment With Study Product | Body Weight - Change From Baseline | Day 7 (n=10, 3) | -0.5 kg | Standard Deviation 1.6 |
| Treatment With Study Product | Body Weight - Change From Baseline | Day 28 (n=10, 2) | 0.6 kg | Standard Deviation 0.9 |
| Treatment With Study Product | Body Weight - Change From Baseline | Day 1 (n=11, 3) | -0.2 kg | Standard Deviation 0.7 |
| Treatment With Placebo | Body Weight - Change From Baseline | Day 28 (n=10, 2) | 0.4 kg | Standard Deviation 0.4 |
| Treatment With Placebo | Body Weight - Change From Baseline | Day 1 (n=11, 3) | -0.6 kg | Standard Deviation 0.4 |
| Treatment With Placebo | Body Weight - Change From Baseline | Day 7 (n=10, 3) | -0.7 kg | Standard Deviation 1.3 |
| Treatment With Placebo | Body Weight - Change From Baseline | Day 14 (n=8, 2) | 0.8 kg | Standard Deviation 0.7 |
| Treatment With Placebo | Body Weight - Change From Baseline | Day 21 (n=6, 2) | 0.5 kg | Standard Deviation 0.1 |
| Treatment With Placebo | Body Weight - Change From Baseline | Day 4 (n=10, 3) | -0.4 kg | Standard Deviation 0.8 |
Secondary
Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline
Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline, Day 7 and Day 28 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 7 (n=10, 3) | -0.4 score on a scale | Standard Deviation 2.3 |
| Treatment With Study Product | Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 28 (n=8, 2) | -0.6 score on a scale | Standard Deviation 1.2 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 7 (n=10, 3) | -3.0 score on a scale | Standard Deviation 3.3 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Average Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 28 (n=8, 2) | -1.3 score on a scale | Standard Deviation 3.2 |
Secondary
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline
Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline, Day 7 and Day 28 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline | Day 7 (n=10, 3) | 0 score on a scale | Standard Deviation 2 |
| Treatment With Study Product | Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline | Day 28 (n=8, 2) | 1 score on a scale | Standard Deviation 2 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline | Day 7 (n=10, 3) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Double-blind Treatment Period - Change From Baseline | Day 28 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
Secondary
Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline
Participants rated the degree to which their pain interfered with various daily functions by using the BPI short form. Interference with general activity was rated on a scale from 0 (does not interfere) to 10 (completely interferes). Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.
Time frame: At baseline and Day 49 during the post-treatment observation period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline | 0 score on a scale | Standard Deviation 1 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Interference of Pain With Aspects of Life (General Activity) During Post-treatment Observation Period - Change From Baseline | 0 score on a scale | Standard Deviation 0 |
Secondary
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline
Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline, Day 7 and Day 28 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 7 (n=10, 3) | -1 score on a scale | Standard Deviation 3 |
| Treatment With Study Product | Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 28 (n=8, 2) | -1 score on a scale | Standard Deviation 3 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 7 (n=10, 3) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Double-blind Treatment Period) - Change From Baseline | Day 28 (n=8, 2) | 1 score on a scale | Standard Deviation 1 |
Secondary
Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline
Participants rated the severity of their pain by using the BPI short form. Pain was rated on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained prior to the start of the dosing on Day 1 of the double-blind dosing period.
Time frame: At baseline and Day 49 during the post-treatment observation period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline | -1 score on a scale | Standard Deviation 5 |
| Treatment With Placebo | Brief Pain Inventory (BPI): Worst Pain Level in Last 24 Hours (Post-treatment Observation Period) - Change From Baseline | 0 score on a scale | Standard Deviation 0 |
Secondary
C Reactive Protein Levels - Change From Baseline
Category title includes number of participants with available data (n) for participants treated with study product.
Time frame: At baseline, Day 1 and Day 7 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | C Reactive Protein Levels - Change From Baseline | Day 1 (n=2) | -1.2 mg/L | Standard Deviation 3 |
| Treatment With Study Product | C Reactive Protein Levels - Change From Baseline | Day 7 (n=1) | NA mg/L | — |
Secondary
Direct Bilirubin - Change From Baseline
Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14, Day 21 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Direct Bilirubin - Change From Baseline | Day 4 (n=10, 3) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Study Product | Direct Bilirubin - Change From Baseline | Day 14 (n= 8, 2) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Study Product | Direct Bilirubin - Change From Baseline | Day 1 (n=11, 3) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Study Product | Direct Bilirubin - Change From Baseline | Day 21 (n=2, 0) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Study Product | Direct Bilirubin - Change From Baseline | Day 7 (n=10, 3) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Study Product | Direct Bilirubin - Change From Baseline | Day 28 (n=10, 2) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Placebo | Direct Bilirubin - Change From Baseline | Day 28 (n=10, 2) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Placebo | Direct Bilirubin - Change From Baseline | Day 1 (n=11, 3) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Placebo | Direct Bilirubin - Change From Baseline | Day 4 (n=10, 3) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Placebo | Direct Bilirubin - Change From Baseline | Day 7 (n=10, 3) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Placebo | Direct Bilirubin - Change From Baseline | Day 14 (n= 8, 2) | 0 mircomoles/L | Standard Deviation 0 |
| Treatment With Placebo | Direct Bilirubin - Change From Baseline | Day 21 (n=2, 0) | NA mircomoles/L | — |
Secondary
Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline
Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 4 (n=9, 3) | -8.5 meters | Standard Deviation 38.2 |
| Treatment With Study Product | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 7 (n=9, 3) | 36.9 meters | Standard Deviation 44.6 |
| Treatment With Study Product | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 14 (n=8, 2) | -0.1 meters | Standard Deviation 31.5 |
| Treatment With Study Product | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 28 (n=8, 2) | -14.9 meters | Standard Deviation 41.2 |
| Treatment With Placebo | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 28 (n=8, 2) | -8.2 meters | Standard Deviation 8.2 |
| Treatment With Placebo | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 4 (n=9, 3) | 20.6 meters | Standard Deviation 8 |
| Treatment With Placebo | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 14 (n=8, 2) | 4.1 meters | Standard Deviation 6.1 |
| Treatment With Placebo | Exercise Tolerance: 6-Minute Walk Distance During the Double-blind Treatment Period - Change From Baseline | Day 7 (n=9, 3) | 28.3 meters | Standard Deviation 24.3 |
Secondary
Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline
Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1.
Time frame: Prior to dosing at baseline and on Day 49 of the post-treatment observation period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline | -20.6 meters | Standard Deviation 41.3 |
| Treatment With Placebo | Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Baseline | -1.1 meters | Standard Deviation 3.5 |
Secondary
Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28)
Functional exercise capacity was evaluated by using the 6-minute walk test (6MWT) which measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes. Guidelines developed by the American Thoracic Society were used for conducting the test and interpreting the results.
Time frame: On last day of double-blind treatment period (Day 28) and on Day 49 of the post-treatment observation period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | -5.6 meters | Standard Deviation 63.6 |
| Treatment With Placebo | Exercise Tolerance: 6-Minute Walk Distance on Day 49 of the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | 7.2 meters | Standard Deviation 4.7 |
Secondary
Exercise Tolerance: Cardiopulmonary Exercise Test [CPET]
CPET was optional, based on capacity of participant to complete the test.
Time frame: On last day of double-blind treatment period (Day 28)
Population: Following an external review and report of CPET capabilities of the external service provider, all CPET testing was suspended and the decision made to not collect or analyze CPET data.
Secondary
Hematocrit Levels - Change From Baseline
Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Hematocrit Levels - Change From Baseline | Day 1 (n=11, 3) | 0.006 L/L | Standard Deviation 0.011 |
| Treatment With Study Product | Hematocrit Levels - Change From Baseline | Day 7 (n=9, 3) | 0.007 L/L | Standard Deviation 0.013 |
| Treatment With Study Product | Hematocrit Levels - Change From Baseline | Day 14 (n=8, 2) | 0.003 L/L | Standard Deviation 0.013 |
| Treatment With Study Product | Hematocrit Levels - Change From Baseline | Day 28 (n=8, 2) | 0.011 L/L | Standard Deviation 0.012 |
| Treatment With Placebo | Hematocrit Levels - Change From Baseline | Day 28 (n=8, 2) | 0.006 L/L | Standard Deviation 0.007 |
| Treatment With Placebo | Hematocrit Levels - Change From Baseline | Day 1 (n=11, 3) | -0.002 L/L | Standard Deviation 0.007 |
| Treatment With Placebo | Hematocrit Levels - Change From Baseline | Day 14 (n=8, 2) | -0.006 L/L | Standard Deviation 0.015 |
| Treatment With Placebo | Hematocrit Levels - Change From Baseline | Day 7 (n=9, 3) | 0.020 L/L | Standard Deviation 0.01 |
Secondary
Hemoglobin Levels - Change From Baseline
A clinical laboratory endpoint that reflects the amount of red blood cells present in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 4, Day 7, Day 14, Day 21 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Hemoglobin Levels - Change From Baseline | Day 1 (n=11, 3) | 0 g/L | Standard Deviation 5 |
| Treatment With Study Product | Hemoglobin Levels - Change From Baseline | Day 4 (n=10, 3) | 1 g/L | Standard Deviation 7 |
| Treatment With Study Product | Hemoglobin Levels - Change From Baseline | Day 7 (n=10, 3) | -1 g/L | Standard Deviation 5 |
| Treatment With Study Product | Hemoglobin Levels - Change From Baseline | Day 14 (n=8, 2) | -2 g/L | Standard Deviation 5 |
| Treatment With Study Product | Hemoglobin Levels - Change From Baseline | Day 21 (n=2, 0) | 1 g/L | Standard Deviation 4 |
| Treatment With Study Product | Hemoglobin Levels - Change From Baseline | Day 28 (n=10, 2) | 0 g/L | Standard Deviation 4 |
| Treatment With Placebo | Hemoglobin Levels - Change From Baseline | Day 21 (n=2, 0) | NA g/L | — |
| Treatment With Placebo | Hemoglobin Levels - Change From Baseline | Day 1 (n=11, 3) | -3 g/L | Standard Deviation 7 |
| Treatment With Placebo | Hemoglobin Levels - Change From Baseline | Day 14 (n=8, 2) | -6 g/L | Standard Deviation 1 |
| Treatment With Placebo | Hemoglobin Levels - Change From Baseline | Day 4 (n=10, 3) | 3 g/L | Standard Deviation 3 |
| Treatment With Placebo | Hemoglobin Levels - Change From Baseline | Day 28 (n=10, 2) | -2 g/L | Standard Deviation 5 |
| Treatment With Placebo | Hemoglobin Levels - Change From Baseline | Day 7 (n=10, 3) | 3 g/L | Standard Deviation 2 |
Secondary
Lactate Dehydrogenase (LDH) Levels - Change From Baseline
LDH levels were measured as a biomarker for intravascular hemolysis. The results are based on the LDH Total measurement. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 1 (n=11, 3) | 60 U/L | Standard Deviation 107 |
| Treatment With Study Product | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 7 (n=9, 3) | 71 U/L | Standard Deviation 101 |
| Treatment With Study Product | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 14 (n=8, 2) | 4 U/L | Standard Deviation 100 |
| Treatment With Study Product | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 28 (n=8, 2) | 29 U/L | Standard Deviation 110 |
| Treatment With Placebo | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 28 (n=8, 2) | -69 U/L | Standard Deviation 91 |
| Treatment With Placebo | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 1 (n=11, 3) | 0 U/L | Standard Deviation 197 |
| Treatment With Placebo | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 14 (n=8, 2) | 689 U/L | Standard Deviation 1142 |
| Treatment With Placebo | Lactate Dehydrogenase (LDH) Levels - Change From Baseline | Day 7 (n=9, 3) | -6 U/L | Standard Deviation 167 |
Secondary
LDH Isoform - Change From Baseline
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 1, Day 7, Day 14 and Day 28
Population: Summary tables for this outcome measure were not done as baseline data missing. Study terminated early.
Secondary
N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline
Category title includes number of participants with available data (n) for participants treated with study product.
Time frame: At baseline, Day 1, Day 7, Day 14 and Day 28 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline | Day 1 (n=7) | 6 pmol/L | Standard Deviation 15 |
| Treatment With Study Product | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline | Day 7 (n=6) | 6 pmol/L | Standard Deviation 97 |
| Treatment With Study Product | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline | Day 14 (n=6) | 32 pmol/L | Standard Deviation 25 |
| Treatment With Study Product | N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) Levels- Change From Baseline | Day 28 (n=7) | 1 pmol/L | Standard Deviation 55 |
Secondary
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21. and Day 28.
Time frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC | -2.352 NPRS score*week | Standard Deviation 2.674 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - AUC | -3.229 NPRS score*week | Standard Deviation 2.847 |
Secondary
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 7, Day 14, Day 21, and Day 28 assessments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 7 (n=11, 3) | 1.682 score on a scale | Standard Deviation 3.482 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 14 (n=10, 2) | -0.850 score on a scale | Standard Deviation 1.255 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 21 (n=8, 2) | -0.825 score on a scale | Standard Deviation 1.302 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 28 (n=9, 2) | 0.689 score on a scale | Standard Deviation 1.279 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 28 (n=9, 2) | -0.650 score on a scale | Standard Deviation 0.071 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 7 (n=11, 3) | 4.533 score on a scale | Standard Deviation 4.536 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 21 (n=8, 2) | -0.650 score on a scale | Standard Deviation 0.071 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Double-blind Treatment Period - Change From Baseline | Day 14 (n=10, 2) | -0.650 score on a scale | Standard Deviation 0.071 |
Secondary
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Area under the curve (AUC) was computed using change from baseline in weekly average values at Day 7, Day 14, Day 21, Day 28, Day 35, Day 42 and Day 49.
Time frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC | -2.836 NPRS score*week | Standard Deviation 3.637 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - AUC | -6.118 NPRS score*week | Standard Deviation 0.874 |
Secondary
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the average of all measures taken from screening through the period prior to start of dosing on Day 1. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Day 35 (n=8, 2) | -4.675 score on a scale | Standard Deviation 3.729 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Day 42 (n=10, 2) | -2.830 score on a scale | Standard Deviation 5.494 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Day 49 (n=9, 2) | -3.089 score on a scale | Standard Deviation 6.049 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Day 35 (n=8, 2) | -7.750 score on a scale | Standard Deviation 1.202 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Day 42 (n=10, 2) | -7.750 score on a scale | Standard Deviation 1.202 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Baseline | Day 49 (n=9, 2) | -8.15 score on a scale | Standard Deviation 0.212 |
Secondary
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28)
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Day 35 (n=8, 2) | -3.425 score on a scale | Standard Deviation 3.302 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Day 42 (n=10, 2) | -1.830 score on a scale | Standard Deviation 4.905 |
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Day 49 (n=9, 2) | -1.978 score on a scale | Standard Deviation 5.479 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Day 35 (n=8, 2) | -7.750 score on a scale | Standard Deviation 1.202 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Day 42 (n=10, 2) | -7.750 score on a scale | Standard Deviation 1.202 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) | Day 49 (n=9, 2) | -8.150 score on a scale | Standard Deviation 0.212 |
Secondary
Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC
Participants assessed their pain levels by using the 0-10 Numeric Rating Scale: 0 = No pain 1-3 = Mild pain (nagging, annoying, interfering little with activities of daily living \[ADLs\]) 4-6 = Moderate pain (interferes significantly with ADLs) 7-10 = Severe pain (disabling; unable to perform ADLs A negative mean change denotes a pain decrease. A positive mean change denotes an increase in pain. Baseline was defined as the most recent value obtained on the last day of the double-blind dosing period (Day 28). Area under the curve (AUC) was computed using change from baseline (Day 28) in weekly average values at Day 35, Day 42 and Day 49.
Time frame: Participants assessed and recorded their pain level daily. Weekly averages were calculated for the Day 35, Day 42 and Day 49 assessments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC | -2.836 NPRS score*week | Standard Deviation 3.637 |
| Treatment With Placebo | Numerical Pain Rating Scale (NPRS): Worst Pain (Weekly Average) in the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period (Day 28) - AUC | -6.118 NPRS score*week | Standard Deviation 0.874 |
Secondary
Oxygen Binding p50/p20 Value - Change From Baseline
A measure of the ability of hemoglobin to bind oxygen. The p50 is the oxygen level at which 50% of the hemoglobin contains oxygen. The p20 is the oxygen level at which 20% of the hemoglobin contains oxygen. Baseline is defined as the most recent value obtained prior to start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: During the double-blind treatment period at baseline, Day 1, Day 4 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Oxygen Binding p50/p20 Value - Change From Baseline | Day 1 (n=11, 3) | 0.0 ratio | Standard Deviation 0.2 |
| Treatment With Study Product | Oxygen Binding p50/p20 Value - Change From Baseline | Day 4 (n=11, 3) | 0.0 ratio | Standard Deviation 0.1 |
| Treatment With Study Product | Oxygen Binding p50/p20 Value - Change From Baseline | Day 7 (n=10, 3) | 0.0 ratio | Standard Deviation 0.2 |
| Treatment With Placebo | Oxygen Binding p50/p20 Value - Change From Baseline | Day 1 (n=11, 3) | 0.0 ratio | Standard Deviation 0.2 |
| Treatment With Placebo | Oxygen Binding p50/p20 Value - Change From Baseline | Day 4 (n=11, 3) | 0.1 ratio | Standard Deviation 0.1 |
| Treatment With Placebo | Oxygen Binding p50/p20 Value - Change From Baseline | Day 7 (n=10, 3) | 0.0 ratio | Standard Deviation 0.1 |
Secondary
Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline
Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. No values available for placebo group for Day 28. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline and once weekly on Days 7, 14, 21, and 28 during the double-blind treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 7 (n=10, 3) | 0 score on a scale | Standard Deviation 1 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 14 (n=9, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 21 (n=8, 2) | 0 score on a scale | Standard Deviation 1 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 28 (n=9, 1) | 0 score on a scale | Standard Deviation 1 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 28 (n=9, 1) | NA score on a scale | — |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 7 (n=10, 3) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 21 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Double-blind Treatment Period - Change From Baseline | Day 14 (n=9, 2) | 0 score on a scale | Standard Deviation 0 |
Secondary
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline
Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | Day 35 (n=8, 2) | 0 score on a scale | Standard Deviation 1 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | Day 42 (n=10, 2) | 0 score on a scale | Standard Deviation 1 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | Day 49 (n=8, 2) | 0 score on a scale | Standard Deviation 1 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | Day 35 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | Day 42 (n=10, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Baseline | Day 49 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
Secondary
Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period
Participants assessed the change in activity limitations, symptoms, emotions, and overall quality of life by using the 1- to 7-point PGIC scale. The question and scale was as follows: Since beginning treatment at this clinic, how would you describe the change in your sickle cell condition? Please circle the number that matches your overall judgment. -3 - much worse -2 - moderately worse -1 - minimally worse 0 - no change +1 - minimally improved +2 - moderately improved +3 - much improved. Baseline was defined as the most recent value obtained on the last day of the double-blind treatment period. Categories contain Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline and once weekly on Days 35, 42, and 49 during the post-treatment observation period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | Day 35 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | Day 42 (n=10, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Study Product | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | Day 49 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | Day 35 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | Day 42 (n=10, 2) | 0 score on a scale | Standard Deviation 0 |
| Treatment With Placebo | Patients´ Global Impression of Change (PGIC) During the Post-treatment Observation Period - Change From Last Day of Double-blind Treatment Period | Day 49 (n=8, 2) | 0 score on a scale | Standard Deviation 0 |
Secondary
Plasma Erythropoietin (EPO) Levels - Change From Baseline
Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow. EPO can be detected and measured in the blood. Baseline defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: At baseline and Day 28 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Study Product | Plasma Erythropoietin (EPO) Levels - Change From Baseline | -5.9 U/L | Standard Deviation 50.3 |
| Treatment With Placebo | Plasma Erythropoietin (EPO) Levels - Change From Baseline | -15.1 U/L | Standard Deviation 20.4 |
Secondary
Reduction in Sickle Cell-specific Complications
Time frame: Throughout the study period (approximately 9 weeks)
Population: Data not collected for this outcome measure. Study terminated early.
Secondary
Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline
A measure of the amount of oxygen in the blood. Oxygen saturation was determined by pulse oximetry. A pulse oximeter was placed over a nail polish-free finger nail to determine peripheral oxygen saturation (SpO2). Baseline was defined as the most recent value obtained prior to the start of dosing on Day 1 of the double-blind treatment period. A mean change from baseline \>0 indicates an increase in oxygen saturation, a mean change \<0 indicates a decrease in oxygen saturation. Category title includes number of participants with available data (n) for participants treated with study product, followed by participants treated with placebo.
Time frame: Prior to, during and after the end of dosing in the double-blind treatment period, i.e., at baseline, Day 4, Day 7, Day 14 and Day 28
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 4 (n=9, 3) | 0 percent saturation | Standard Deviation 2 |
| Treatment With Study Product | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 7 (n= 9, 3) | 0 percent saturation | Standard Deviation 2 |
| Treatment With Study Product | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 14 (n=8, 2) | 0 percent saturation | Standard Deviation 2 |
| Treatment With Study Product | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 28 (n=8, 2) | 0 percent saturation | Standard Deviation 3 |
| Treatment With Placebo | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 28 (n=8, 2) | 6 percent saturation | Standard Deviation 8 |
| Treatment With Placebo | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 4 (n=9, 3) | 4 percent saturation | Standard Deviation 5 |
| Treatment With Placebo | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 14 (n=8, 2) | 8 percent saturation | Standard Deviation 10 |
| Treatment With Placebo | Resting Oxygen Saturation as Measured by Oximetry (SpO2) - Change From Baseline | Day 7 (n= 9, 3) | -4 percent saturation | Standard Deviation 8 |
Secondary
Reticulocyte Percent- Change From Baseline
Category title includes number of participants with available data (n) for participants treated with study product.
Time frame: At baseline, Day 1 and Day 7 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Reticulocyte Percent- Change From Baseline | Day 1 (n=2) | -0.46 percent | Standard Deviation 0.18 |
| Treatment With Study Product | Reticulocyte Percent- Change From Baseline | Day 7 (n=1) | NA percent | — |
Secondary
Serum Ferritin Levels - Change From Baseline
Time frame: At baseline, Day 1 and Day 7 during the double-blind treatment period
Population: Participants who provided baseline data and at least one other data point for this outcome measure. Summary tables for placebo group not done as data not collected. Study terminated early.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment With Study Product | Serum Ferritin Levels - Change From Baseline | Day 1 | -4.9 mircograms/L | Standard Deviation 0.1 |
| Treatment With Study Product | Serum Ferritin Levels - Change From Baseline | Day 7 | NA mircograms/L | — |